Methods and compositions for producing hydrogel capsules coated for low permeability and physical integrity

ABSTRACT

Methods and compositions for producing hydrogel capsules enveloped with at least one coating layer is disclosed. The coating formulations deposited on the surface of the capsules can improve the physical integrity and the water-retention properties of the alginate beads. The coating formulations can be sequentially applied in various combinations to obtain desirable properties, such as improved physical integrity, mechanical strength, and low permeability, that can extend the shelf-life of the capsules when incorporated into various consumer products.

BACKGROUND

Hydrogels, formed as capsules, have been adapted as carrier devices forholding/delivering various molecules of interest that can be depositedwithin the core spaces of hydrogels. Typically, due to technicallimitations, the molecules of interest were suspended in oil-basedsolvents resulting in a capsule structure comprising a hydrophobic coreenclosed by a hydrophilic hydrogel matrix that can support substantialamounts of water (e.g., at least 70%). Such hydrogels comprising ahydrophobic core can be of limited use for many applications. Thedevelopment of more advanced hydrogels comprising a hydrophilic corehave been challenging because such capsules cannot maintain the phaseseparation between the hydrophilic core and the hydrophilic-hydrogelshell matrix, resulting in hydrogel capsules that exhibit sub-optimalproperties, and therefore, are inadequate for long-term storage and/orprolonged usage.

SUMMARY

In various embodiments, methods and compositions for producing hydrogelcapsules (for example, comprising alginate) enveloped with at least onecoating layer are disclosed. Various embodiments are directed totobacco-containing smokable and smokeless products comprising hydrogelcapsules coated with at least one coating layer formulated as disclosed.Various embodiments are directed to tobacco-free consumer productscomprising hydrogel capsules coated with at least one coating layerformulated as disclosed. The coating formulations deposited on thesurface of hydrogel capsules can improve the physical integrity and thewater-retention properties of the hydrogel capsules. The coatingformulations can be sequentially applied in various combinations toobtain desirable properties, such as improved physical integrity,mechanical strength, and low permeability, that can extend theshelf-life of hydrogel capsules when incorporated into various consumerproducts.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic of a basic configuration of an hypotheticalhydrogel capsule without a protective coating, which may berepresentative of similar structures disclosed in the prior art.

FIG. 2 is a schematic of a hydrogel capsule protected by at least onecoating layer.

FIG. 3A is a schematic of a hydrogel capsule protected by at least onecoating layer comprising a film-forming material.

FIG. 3B is a schematic of a hydrogel capsule protected by at least onecoating layer comprising a wax.

FIG. 4 is a schematic of a hydrogel capsule protected by at least twocoating layers.

FIG. 5A is a schematic of a pouched tobacco product comprising a singlehydrogel capsule protected by at least one coating layer.

FIG. 5B is a schematic of a pouched tobacco product comprising multiplehydrogel capsules, each protected by at least one coating layer.

FIG. 6A is an image of an exemplary alginate (Alg) hydrogel capsulecoated with Eudragit® L30D-55 (a methacrylic acid-co-ethyl acrylatelatex referred to herein as “Eud”) to form Eud-Alg hydrogel. FIG. 6B isan image of an exemplary hydrogel capsule, first coated with Eudragit®L30D-55, and coated subsequently with a wax formulation to formWax-Eud-Alg hydrogel, as described in Example 2.

FIGS. 7A and 7C show a cross-sectional analysis of Eud-Alg hydrogelcapsule as determined by environmental scanning electron microscopy(“ESEM”). FIG. 7B is an EDS spectrum of Eud-Alg hydrogel capsule. FIGS.7D-7F show cross-sectional analysis of Eudragit® coating to determine Caand Na content by x-ray line scans, as described in Example 3.

FIG. 8A shows the surface morphology of an exemplary Eud-Alg hydrogelcapsule, as described in Example 4.

FIG. 8B shows the surface morphology of an exemplary 12% ACAP-Eud-Alghydrogel capsule, in which “ACAP” represents (acrylamidomethyl)celluloseacetate propionate, as described in Example 4.

FIG. 8C shows the surface morphology of an exemplary Eud-Alg hydrogelcapsule exposed to 120° C. for 5 min, as described in Example 4.

FIG. 9 shows Fourier transform infrared spectroscopy (“FTIR”) graphs forvarious coating formulations, including a coating layer formulated with(acrylamidomethyl)cellulose acetate propionate (“ACAP”) (as graph “A”),a coating layer formulated with Eudragit® L30D-55 (“Eud”) (as graph“B”), and double-coated layers of ACAP-Eud that were sequentiallydeposited (as graph “C”), as described in Example 5.

FIG. 10 shows differential scanning calorimetry (“DSC”) graphs forvarious coating formulations, including a coating layer formulated withEudragit® L30D-55 (as curve “Eud”), a coating layer formulated with(acrylamidomethyl)cellulose acetate propionate (as curve “ACAP”), anddouble-coated layers of ACAP-Eud that were sequentially deposited (ascurve “ACAP-Eud”), as described in Example 6.

FIG. 11 shows water-retention profiles, expressed as % weight retention,for various hydrogels tested, including alginate hydrogel capsules (“AlgBead”), Eud-coated alginate hydrogel capsules (“Eud-Alg Bead”), alginatehydrogel capsules coated with 12% ACAP-Eud (“12% ACAP-Eud-Alg Bead”),and alginate hydrogel capsules coated with 24% ACAP-Eud-Alg (“24%ACAP-Eud-Alg Bead”) respectively, measured at room conditions of 23° C.and RH 50%, as described in Example 7.

FIG. 12 shows short-term (5 hours) and long-term (3 days)water-retention profiles, expressed as % weight retention, forEud-coated alginate hydrogel capsules that were exposed to different pHconditions after coating with Eudragit®, measured at 23° C. and RH 50%,as described in Example 8.

FIG. 13A shows the effect on the surface morphology of Eud-Alg hydrogelcapsules exposed to pH 1.6 condition after coating with Eudragit®, asdescribed in Example 8.

FIG. 13B shows the effect on the surface morphology of Eud-Alg hydrogelcapsules exposed to pH 4.6 condition after coating with Eudragit®, asdescribed in Example 8.

FIG. 14 shows short-term (5 hours) and long-term (3 days)water-retention profiles, expressed as % weight retention, forEud-coated alginate hydrogel capsules that were exposed to differentthermal exposure after coating with Eudragit®, measured at 23° C. and RH50%, as described in Example 9.

FIG. 15 shows water-retention profiles, expressed as % weight retention,for ACAP-Eud-coated alginate hydrogel capsules that were exposed to 60°C. for 10 min, after coating with Eudragit®, measured at 23° C. and RH50%, as described in Example 9.

FIG. 16A shows the surface morphology of ACAP-Eud-Alg hydrogel capsulesnot exposed to heat, as described in Example 9.

FIG. 16B shows the surface morphology of ACAP-Eud-Alg hydrogel capsulesexposed to 60° C. for 10 min, as described in Example 9.

FIG. 17 shows water-retention profiles, expressed as % weight retention,for various combinations of coating formulations deposited on thesurface of alginate hydrogel capsules, measured at room conditions 23°C. and RH 50%, as described in Example 10.

DETAILED DESCRIPTION I. Definitions

Throughout this disclosure and the appended claims, the terms “a” and“the” function as singular and plural referents unless the contextclearly dictates otherwise. Thus, for example, a reference to “a core”includes a plurality of such cores, and a reference to “the hydrogelcapsule” includes reference to one or more of such hydrogel capsules.

The term “hydrogel” refers to any network of polymer chains crosslinkedtogether for stabilization, and is amenable to shaping into a desirableform (e.g., spherical, disk, elliptical, pod-like). Hydrogels includecolloidal gels that can hold substantial amounts of water. Alginate is apreferred hydrogel. Other hydrogels include pectins and carrageenan.

As used herein, the term “about” when used in conjunction with a statednumerical value or range denotes somewhat more or somewhat less than thestated value or range, to within a range of ±10% of that stated.

The term “capsule” refers to a structure comprising at least onecontinuous surface of a material enclosed together to form at least onecore in the interior space of the capsule. The terms capsule and beadare used interchangeably herein. In the simplest embodiment, the capsulecomprises a single core, sufficient to carry a molecule of interest or acombination of molecules of interest.

The term “hydrophilic” refers to a charge-polarized molecule that, viahydrogen bonding, can associate more readily with water (or dissolvemore readily in water) than with (or in) oil or other hydrophobicsolvents. Hydrophilic molecules are typically positively or negativelycharged, or zwitterionic, and include solute molecules and solventmolecules. Examples of hydrophilic molecules include water molecules,colloids, and any water-soluble molecules, such as alcohols.

The term “hydrophobic” refers to a neutrally-charged molecule, andincludes non-polar solute molecules and non-polar solvent molecules. Inwater, hydrophobic molecules can cluster together to form micelles.Examples of hydrophobic molecules include alkanes, oils, and fats.

The terms “coating” or “coating layer” or “film” or “film layer” areinterchangeably used. A coating layer may be deposited onto the surfaceof hydrogel capsules. A coating layer may be deposited onto the surfaceof another coating layer, in which case the “first” coating layer isapplied before the “second” coating layer.

The term “tobacco” refers to any variety of the genus Nicotiana, andincludes native tobacco variants, transgenic tobacco variants, andcultured tobacco grown in vitro. Exemplary species of tobacco include N.rustica, N. tabacum (e.g., LA B21, LN KY171, TI 1406, Basma, Galpao,Perique, Beinhart 1000-1, and Petico). Other species include N. acaulis,N. acuminata, N. acuminata var. multiflora, N. africana, N. alata, N.amplexicaulis, N. arentsii, N. attenuata, N. benavidesii, N.benthamiana, N. bigelovii, N. bonariensis, N. cavicola, N. clevelandii,N. cordifolia, N. corymbosa, N. debneyi, N. excelsior, N. forgetiana, N.fragrans, N. glauca, N. glutinosa, N. goodspeedii, N. gossei, N. hybrid,N. ingulba, N. kawakamii, N. knightiana, N. langsdorffii, N. linearis,N. longiflora, N. maritima, N. megalosiphon, N. miersii, N. noctiflora,N. nudicaulis, N. obtusifolia, N. occidentalis, N. occidentalis subsp.hesperis, N. otophora, N. paniculata, N. pauciflora, N. petunioides, N.plumbaginifolia, N. quadrivalvis, N. raimondii, N. repanda, N. rosulata,N. rosulata subsp. ingulba, N. rotundifolia, N. setchellii, N. simulans,N. solanifolia, N. spegazzinii, N. stocktonii, N. suaveolens, N.sylvestris, N. thyrsiflora, N. tomentosa, N. tomentosiformis, N.trigonophylla, N. umbratica, N. undulata, N. velutina, N. wigandioides,and N.×sanderae. The tobacco may be whole, shredded, cut, cured, aged,fermented, or otherwise processed, e.g., granulated or encapsulated.Tobacco may also be in the form of finished products, including anynon-combustible tobacco that can be orally consumed, e.g., smokelesstobacco and lit-end smokable products, such as cigars and cigarettes.

II. Formulations for Manufacturing Hydrogel Capsules

FIG. 1 is a schematic of a basic configuration of a hypotheticalhydrogel capsule without a protective coating, which may berepresentative of similar structures disclosed in the prior art. In FIG.1, the hydrogel capsule 100 comprises a core component (“core”) 110enclosed by a hydrogel matrix (“shell”) 120. If molecules of interestare suspended in a hydrophobic solvent (e.g., oil) and deposited withinthe core 110 of the capsule, then the capsule is more likely to retainthe initial physical integrity/shape defined at the time of manufacturedue to inherent repulsive forces between the “hydrophobic” core and the“hydrophilic” shell. In contrast, if molecules of interest are suspendedin a “hydrophilic” solvent (e.g., water) and deposited within the core110 of the capsule, then the physical integrity/shape of the capsule ismore likely to deviate substantially from the initial state (i.e.,defined at the time of manufacture). After prolonged storage and/orprolonged use, the physical boundary between the hydrophilic core andthe hydrophilic shell become less-defined. Furthermore, a hydrogelcapsule comprising a hydrophilic core may be unsuitable to carryunstable molecules that are more likely to be inactivated (e.g.,precipitation or aggregation of molecules of interest) if theconcentration of these molecules increases due to water loss viaevaporation. Thus, improvements in the manufacture of both types ofhydrogel capsules are highly desirable.

The figures and examples herein provide: (1) exemplary formulations andmethods for incorporating molecules of interest into the core ofhydrogel capsules; (2) exemplary formulations and methods formanufacturing the hydrogel matrix/shell; and (3) exemplary formulationsand methods for coating the hydrogel matrix/shell. Hydrogel capsules canbe incorporated into various consumable products, including: (a)tobacco-containing products, such as (i) smoking tobacco products and(ii) smokeless tobacco products; and (b) consumable products withouttobacco. Other uses include controlled release of active agents (such asnutraceuticals, water soluble flavors or drugs), cell immobilization,cell delivery, or cell storage. Coating formulations can be employed inthe manufacture of: (a) hydrogel capsules comprising a hydrophilic core,and (b) hydrogel capsules comprising a hydrophobic core, although theexamples may be described in the context of hydrogel capsules of type(a). The coating formulations can be sequentially applied in variouscombinations to obtain desirable properties. For example, the physicalintegrity, the mechanical strength, and the capacity for water retentionof the capsules can be controlled. The improved shell/coating structuredisclosed herein can overcome problems such as undesired swelling anddissolving of alginate capsules, thereby improving the shelf-life of thecapsules, which is helpful for their incorporation into various consumerproducts.

FIG. 2 is a schematic of a hydrogel capsule protected by at least onecoating layer. In FIG. 2, an exemplary hydrogel capsule 200 is shown,comprising: a core 210, a hydrogel matrix/shell 220, and one coatinglayer 230 that envelops the exterior surface of the hydrogelmatrix/shell 220. The coating layer 230 can serve as a protective layeror a protective film to maintain or to strengthen the physical integrityof the hydrogel capsule. The coating layer 230 can reduce thepermeability of the hydrogel capsule by serving as a physical barrierthat can prevent the diffusion of water molecules from the exteriorsurface of the hydrogel matrix/shell 220. If the hydrogel capsulecomprises a hydrophilic core, then water molecules from the hydrophiliccore 210 will tend to diffuse into the hydrogel matrix/shell 220 toreplace the water molecules that have evaporated from the surface of thehydrogel matrix/shell 220, which would result in shrinkage of thehydrogel capsule 200. If the coating layer 230 deposited on the surfaceof the hydrogel shell 220 is not effective, shrinkage of the hydrogelcapsule 200 may occur, and cracks and other deformation of the coatinglayer 230 may result. FIGS. 6A, 8A, 8C, 13A, and 13B illustrate theeffectiveness of depositing Eudragit® as a coating layer for protectingalginate hydrogel capsules as determined by optical imaging or surfacemorphology analysis.

A. Exemplary Core Additives

Various molecules of interest can be included as additive components ofthe core within the hydrogel capsules, including various flavor agents,sensates, sequestering agents, coloring agents, plasticizing agents,complexing agents, filling agents, natural and/or artificial sweeteners,binders, thickening agents, souring agents, pigments, surfactants,stabilizing agents, antioxidants, preservatives, humectants,medicaments, tobacco, tobacco extracts, equivalents, and other additivesas described below.

The term “controlled-release” refers to the capacity to control therelease profile of an encapsulation device, such as hydrogel capsulesdescribed herein. Any of these components can be encapsulatedindividually, or as a combination, into smaller capsules in order tocontrol the release profile for any component as desired. For example,if a fast-release profile is desired for a first flavorant of interest,then the porosity of the polymer constituting the capsules can beincreased. In contrast, if a slow-release profile is desired for asecond flavorant of interest, then the porosity of the polymerconstituting the capsules can be decreased.

1. Flavorants and Sensates

Suitable flavorants, which may generate taste and/or aroma, include anynatural or synthetic flavorant, such as tobacco, smoke, menthol, mint,such as peppermint and spearmint, chocolate, licorice, citrus and otherfruit flavorants, gamma octalactone, vanillin, ethyl vanillin, breathfreshener flavorants, spice flavorants such as cinnamon, methylsalicylate, linalool, bergamot oil, geranium oil, lemon oil, and gingeroil. Other suitable flavorants may include flavorant compounds selectedfrom the group consisting of an acid, an alcohol, an ester, an aldehyde,a ketone, a pyrazine, combinations thereof and equivalents. Suitableflavorant compounds may be selected, for example, from the groupconsisting of phenylacetic acid, solanone, megastigmatrienone,2-heptanone, benzylalcohol, cis-3-hexenyl acetate, valeric acid, valericaldehyde, ester, terpene, sesquiterpene, nootkatone, maltol,damascenone, pyrazine, lactone, anethole, iso-valeric acid, combinationsthereof and equivalents. In addition, flavorants can also beencapsulated for controlled delivery. Exemplary additional natural andartificial flavorants include peppermint, spearmint, wintergreen,menthol, cinnamon, chocolate, vanillin, licorice, clove, anise,sandalwood, geranium, rose oil, vanilla, lemon oil, cassia, spearmint,fennel, ginger, ethylacetate, isoamylacetate, propylisobutyrate,isobutylbutyrate, ethylbutyrate, ethylvalerate, benzylformate, limonene,cymene, pinene, linalool, geraniol, citronellol, citral, peppermint oil,orange oil, coriander oil, borneol, fruit extract, and equivalents. In apreferred embodiment, flavorant agents include essential oils andessences of coffee, tea, cacao, and mint. A suitable amount of aflavorant present in the core ranges from about 0.001 wt % to about 50wt %. In a preferred embodiment, the amount ranges from about 1 wt % toabout 40 wt %. In a preferred embodiment, the amount ranges from about10 wt % to about 30 wt %. The flavorant may be incorporated as a solidpowder, sprayed dried as a liquid, or mixed with starch or gum-typematrix.

Sensates are ingredients that can induce a sensorial experience, such astingling, sensation of warmth, sensation of cooling, and equivalents.Suitable sensates include sensate agents such as acetic acid, adipicacid, citric acid, lactic acid, maleic acid, succinic acid, tartaricacid, equivalents and mixtures thereof. A suitable amount of a sensateagent ranges from about 0.001 wt % to about 5 wt %. In a preferredembodiment, the amount of sensate agent ranges from about 0.1 wt % toabout 2 wt %.

2. Sequestering Agents

For embodiments wherein the alginate capsules include tobacco,sequestering agents can be employed for binding components of tobacco ortobacco extracts, such as tobacco-specific nitrosamines (“TSNAs”) withinthe core of the hydrogel capsule. Sequestering agents can be effectivein reducing the diffusion or transport of certain TSNAs from varioustobacco-containing products (e.g., pouched products) into a consumer'smouth. Suitable sequestering agents include polyvinylpolypyrrolidone. Asuitable amount of sequestering agent ranges from 0.001 up to about 5 wt%, and more preferably ranges up to about 2 wt %.

3. Antioxidants and Preservatives

The capsules can optionally include antioxidants and/or preservatives.Exemplary antioxidants include ascorbic acid, vitamin E, and sodiumpyrosulfate. Exemplary preservatives include acetic acid, benzoic acid,citric acid, lactic acid, malic acid, sorbic acid, and tartaric acid. Asuitable amount of an antioxidant and/or preservative ranges from 0.001up to about 5 wt %, and more preferably ranges up to about 2 wt %.

4. Tobacco/Tobacco Extracts and Tobacco Capsules

In an embodiment, the capsules can include a tobacco component. Any rawor processed forms of tobacco, e.g., as a powder/dust, a granule, ashred, a slurry, a flowable gel, and equivalents can be added to thecapsules. The final tobacco concentration in the capsules ranges from 1percent to 99 percent by weight of the final composition, for example,and ranges at most from about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%,50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% tobacco. In anembodiment, the alginate capsules include about 20 to 30% tobacco.

Humectants can be employed for maintaining and protecting the moisturelevels of the tobacco material in tobacco-containing hydrogel capsules.Humectants can be employed as preservatives to remove excess water andthereby, reduce the growth of micro-organisms. Humectants can beemployed for providing a higher moisture feel in a drier tobaccomaterial (or tobacco substitute material) or a drier smokeless tobaccomaterial. Examples of humectants include glycerol and propylene glycol.A suitable amount of a humectant ranges from about 0.001 wt % to about 5wt %. More preferably, the amount ranges from about 0.1 wt % to about 2wt %.

Exemplary binders include mono based or polysaccharide based materials,modified cellulosics, starches, and/or cellulose ethers. A suitableamount of a binder ranges from 0.001 up to about 20 wt %, and morepreferably the amount ranges up to about 10 wt %. Exemplary thickeningagent include polymers such as polyvinyl pyrrolidone and polyvinylalcohol, and gums such as xanthan gum, gum arabic, and acacia gum.Generally, the stiffness of capsules can be increased and thedissolution rate (i.e., dissolution upon exposure to moisture) can bedecreased by increasing the average molecular weight of polymers thatform a film. Thickening agents can be added to the core of the capsulesto increase the modulus (i.e., stiffness) of the capsules and to reducethe deformation of capsules during/after the drying step (e.g., duringstorage). A suitable thickening agent ranges from 0.001 up to about 20wt. %, and more preferably ranges from 0.001 up to about 5 wt. % of thefinal dried composition.

5. Other Components

The capsules can optionally contain medicaments, nutraceuticals, and/orcosmetics. Examples thereof include vitamins, perfumes, and ointments.

The capsules can optionally contain products not intended for humanconsumption, for example agrochemicals, disinfectants, detergents, anddyestuff.

Filling agents can be employed for controlling the physical propertiesof the hydrogel capsule (e.g., texture, weight, etc.). Exemplary fillingagents include cellulose, titanium oxide, magnesium silicate (e.g.,talc), aluminum silicate, magnesium carbonate, calcium carbonate (e.g.,limestone), calcium phosphate, calcium sulfate, zinc oxide, aluminumoxide, equivalents, equivalents, and mixtures thereof. Filling agentssuch as carbonate and phosphate salts can also be used to adjust the pH.In a preferred embodiment, the pH of the capsules is greater than 5,more preferably greater than 6 (e.g., greater than 6.5, 7, or 7.5). Thefilling agents can be incorporated in an amount up to about 50 wt. %.

Suitable natural and/or artificial sweeteners include water solublesweeteners such as monosaccharides, disaccharides, and polysaccharides(e.g., xylose, ribose, sucrose, maltose, fructose, glucose, maltose,mannose). A suitable amount of a sweetener ranges from about 0.001 wt %to about 5 wt %. In a preferred embodiment, the amount of a sweetenerranges from about 0.1 wt % to about 2 wt %.

Plasticizing agents can be employed for controlling the stiffness andthe viscosity of a polymer melt during casting or extrusion. Exemplaryplasticizing agents include monoacetin; diacetin; triacetin; glycolssuch as polyethylene glycol and propylene glycol; polyhydric alcoholssuch as glycerin and sorbitol; mineral oils; vegetable oils; glyceroland glycerol esters such as glycerol triacetate. A suitable amount of aplasticizing agent ranges from 0.001 up to about 20 wt. %, and morepreferably ranges up to about 5 wt. %.

Exemplary stabilizing agents include various gums such as guar gum,xanthan gum, locust bean gum, and carrageenan. A suitable amount of astabilizing agent ranges from 0.001 up to 10 wt. %, and more preferablyranges up to about 2 wt. % of the final composition.

Suitable surfactants include mono and diglycerides of fatty acids,lactylates, pluronic acid, polyoxyethylene sorbitol esters, latanol,sodium lauryl sulfate, and equivalents. A suitable amount of surfactantsranges from 0.001 up to about 10 wt. %, and more preferably ranges up toabout 2 wt. % of the final composition.

Suitable pigments or coloring agents can be incorporated in an amountfrom 0.001 up to about 5 wt. % of the final composition.

B. Production of Hydrogel Matrix/Shell

For manufacturing hydrogel matrix/shell, suitable crosslinkable polymersinclude alginates, pectins, carrageenan, and equivalents thereof. Anexemplary formulation for producing an alginate hydrogel is provided inExample 1. The various components suitable for incorporation into thecore component can be suitable for incorporation into the hydrogelmatrix/shell (e.g., flavorants, pigments).

A crosslinked polymer can be obtained by various methods, including byionic gelation, in which ions are added to a suspension of the monomersof a suitable polymer. Examples of ions suitable to activate ionicgelation include, sodium, potassium, calcium, aluminum, lanthanum,magnesium, and barium. A suitable amount of a polymer ranges in anamount up to about 95 wt %, more preferably from about 0.5 wt % to about85 wt %, and most preferably from about 10 wt % to about 75 wt % basedon the total weight of hydrogel matrix/shell. The rate of diffusion ofcomponents contained in the core can be controlled by adjusting thethickness and/or porosity of the matrix/shell. For example, if alginatehydrogel capsules are manufactured, then the porosity of matrix/shell(i.e., crosslinking density) can be controlled by adjusting the ratio ofmannuronic units to guluronic units (M:G) to form the alginate polymer.For example, to obtain a fluid-like consistency, themannuronic:guluronic ratio should be greater than 1:1, and the ratio mayrange from about 1.5-3:1. In contrast, to obtain a gel-like consistency,the mannuronic:guluronic ratio should be less than 1:1, and the ratiomay range from about 0.4:1-0.6:1.

C. Exemplary Coating Formulations and Coating Configurations

In the following, FIGS. 3A, 3B, and 4 provide exemplary coatingconfigurations that have been described further in Examples 1-10. Thevarious components suitable for incorporation into the core componentcan be suitable for incorporation into a coating layer (e.g.,flavorants, pigments, souring agents).

FIG. 3A is a schematic of a hydrogel capsule protected by at least onecoating layer comprising a film-forming material. In FIG. 3A, anexemplary hydrogel capsule 300 is shown, comprising: a core 310comprising one or more components as described herein, a hydrogelmatrix/shell 320 of one or more polymer materials as described herein,and one coating layer 330 of one or more coating materials as describedherein that envelops the exterior surface of the hydrogel matrix/shell320. In an embodiment, a hydrogel capsule comprises: a core; a hydrogelmatrix/shell; and a coating layer such as a film-forming latex thatcompletely envelops the exterior surface of the hydrogel matrix/shell.As another example, a hydrogel capsule may comprise: a core thatincludes at least one core component such as a flavorant and/or sensate;a hydrogel matrix/shell; and a coating layer comprising a film-forminglatex that completely envelops the exterior surface of the hydrogelmatrix/shell.

According to one embodiment, a tobacco-containing hydrogel capsulecomprises: a core that includes tobacco and/or tobacco extract; ahydrogel matrix/shell selected from the group consisting of alginates,pectins, and carrageenan; and a single coating layer selected from thegroup consisting of Eudragit® L30D-55 and (acrylamidomethyl)celluloseacetate propionate (ACAP). Various embodiments are directed to atobacco-containing hydrogel capsule, comprising: a core that includestobacco, tobacco extract, and/or a sequestration agent; a hydrogelmatrix/shell selected from the group consisting of alginates, pectins,and carrageenan; and a single coating layer selected from the groupconsisting of Eudragit® L30D-55 and (acrylamidomethyl)cellulose acetatepropionate (ACAP).

FIG. 3B is a schematic of a hydrogel capsule protected by at least onecoating layer comprising a wax. In FIG. 3B, an exemplary hydrogelcapsule 350 is shown, comprising: a core 360 comprising one or morecomponents as described herein, a hydrogel matrix/shell 370 of one ormore polymer materials as described herein, and a single coating layer380 of one or more coating materials as described herein that envelopsthe exterior surface of the hydrogel matrix/shell 370. In variousembodiments, a hydrogel capsule comprises: a core; a hydrogelmatrix/shell; and a single coating layer comprising a wax thatcompletely envelops the exterior surface of the hydrogel matrix/shell.In various embodiments, a hydrogel capsule comprises: a core thatincludes at least one flavorant and/or sensate; a hydrogel matrix/shell;and a single coating layer comprising a wax that completely envelops theexterior surface of the hydrogel matrix/shell.

According to one embodiment, a tobacco-containing hydrogel capsulecomprises: a core that includes tobacco and/or tobacco extract; ahydrogel matrix/shell selected from the group consisting of alginates,pectins, and carrageenan; and a single coating layer selected from thegroup consisting of paraffin wax, carnauba wax, and polyester wax.Various embodiments are directed to a tobacco-containing hydrogelcapsule, comprising: a core that includes tobacco, tobacco extract,and/or a sequestration agent; a hydrogel matrix/shell selected from thegroup consisting of alginates, pectins, and carrageenan; and a singlecoating layer selected from the group consisting of paraffin wax,carnauba wax, and polyester wax.

FIG. 4 is a schematic of a hydrogel capsule protected by at least twocoating layers. In FIG. 4, an exemplary hydrogel capsule 400 is shown,comprising: a core 410 comprising one or more components as describedherein, a hydrogel matrix/shell 420 of one or more polymer materials asdescribed herein, a first coating layer 430 of one or more coatingmaterials as described herein that envelops the exterior surface of thehydrogel matrix/shell 420, and a second coating layer 440 of one or morecoating materials as described herein that envelops the exterior surfaceof the hydrogel matrix/shell 430.

Various embodiments are directed to a hydrogel capsule, comprising: acore; a hydrogel matrix/shell; a first coating layer comprising a firstfilm-forming material that envelops the exterior surface of the hydrogelmatrix/shell; and a second coating layer comprising a secondfilm-forming material that envelops the exterior surface of the firstcoating layer. Various embodiments are directed to a hydrogel capsule,comprising: a core that includes at least one flavorant and/or sensate;a hydrogel matrix/shell such as alginate, pectin and/or carrageenan; afirst coating layer comprising a first film-forming material thatenvelops the exterior surface of the hydrogel matrix/shell; and a secondcoating layer comprising a second film-forming material such as a wax orlatex film that envelops the exterior surface of the first coatinglayer.

According to one embodiment, a hydrogel capsule comprises: a core; ahydrogel matrix/shell selected from the group consisting of alginates,pectins, and carrageenan; a first coating layer comprising a firstfilm-forming material that envelops the exterior surface of the hydrogelmatrix/shell; and a second coating layer selected from the groupconsisting of paraffin wax, carnauba wax, and polyester wax.

According to another embodiment, a tobacco-containing hydrogel capsulecomprises: a hydrogel capsule comprising: a core that includes tobaccoand/or tobacco extract and optionally a sequestration agent, flavorantand/or sensate; a hydrogel matrix/shell; a first coating layercomprising a film-forming material that envelops the exterior surface ofthe hydrogel matrix/shell; and a second coating layer comprising a waxthat envelops the exterior surface of the first coating layer.

III. Smokeless Tobacco Products

Various embodiments are directed to smokeless tobacco products,comprising at least one hydrogel capsule as described throughout thisdisclosure. Examples of smokeless tobacco products include snuff (moistor dry), chewing tobacco, loose tobacco, pouched tobacco, andequivalents. The disclosed smokeless tobacco products have a number ofadvantages, including longer shelf-life, improved taste, improvedsensorial experience, and prolonged enjoyment in the use of suchproducts due to the encapsulation of tobacco and other components.Tobacco and tobacco extracts can be interchangeably utilized.

The size, shape, and configuration of hydrogel capsules that can beincorporated into various smokeless pouched tobacco products can varysubstantially. The following FIGS. 5A-5D provide examples of suchproducts.

FIG. 5A is a schematic of a pouched tobacco product comprising a singlehydrogel capsule protected by at least one coating layer. In FIG. 5A,the pouch product 500 comprises: a porous membrane 510 that encloses asingle hydrogel capsule 512 comprising a hydrogel matrix/shell 516 thatencloses a core 514 that includes a tobacco material, a flavorant, asensate, and/or a sequestration agent. Alternatively, the tobaccomaterial can be further encapsulated.

FIG. 5B is a schematic of a pouched tobacco product comprising multiplehydrogel capsules, each protected by at least one coating layer. In FIG.5B, the pouch product 520 comprises: a porous membrane 522 that enclosesmultiple hydrogel capsules, such as 524 and 526, wherein each hydrogelcapsule comprising a hydrogel matrix/shell that encloses a core thatincludes a tobacco material, a flavorant, a sensate, and/or asequestration agent.

IV. Smokable Tobacco Products

Various embodiments are directed to smokable tobacco products,comprising at least one hydrogel capsule as described throughout thisdisclosure. The disclosed smokable tobacco products have a number ofadvantages, including longer shelf-life, improved taste, improvedsensorial experience, and prolonged enjoyment in the use of suchproducts due to the encapsulation of tobacco and other components.Tobacco and/or tobacco extracts can be utilized.

The hydrogel capsules can be incorporated into the filters of varioussmoking products, such as cigars and cigarettes. The smoking articleshave a longer shelf-life because the volatile flavors and sensates canbe stabilized within the core of the capsules, due to at least onecoating later that reduces the permeability of the hydrogel capsule.During smoking, the essence of tobacco, flavorants, and sensates can bereleased at different time points and prolong the enjoyment of thesmoking article. The composition of the hydrogel matrix can be modifiedin order to obtain a desirable flavorant-release profile.

V. Consumer Products without Tobacco

Various embodiments are directed to tobacco-free consumer productscomprising at least one hydrogel capsule as described throughout thisdisclosure.

EXAMPLES Example 1 Preparation of Calcium Alginate Hydrogel Capsules andExemplary Coating Formulations

Alginate hydrogel capsules impregnated with water molecules can beformed by cross-linking together alginate polymer chains in a reactionmediated by Ca²⁺ ions that can enter the electronegative, inter-chaincavities of the alginate polysaccharide promoting the formation ofrod-like, cross-linked matrix structure. As an example, 4-5 mm diameteralginate hydrogel capsules were formed by reacting together 2% sodiumalginate aqueous solution at pH 7.7 and 5% CaCl₂ solution at pH 7.0. Atransfer pipette (with an opening of approximately 4 mm in diameter) wasused to dispense 25 ml of 2% sodium alginate aqueous solution asdroplets into 30 ml of 5% CaCl₂ solution. The mixture was stirred usinga magnetic stirrer at 260 rpm for 30 seconds to form water-impregnatedalginate hydrogel capsules (Alg) with a diameter of approximately 4 mm.The hydrogel capsules were then transferred into 200 ml of distilledwater and stirred using a magnetic stirrer at 260 rpm for 3 min to stopthe alginate cross-linking reaction with the calcium ions. Thesecross-linked hydrogel capsules contained approximately 97% water contentby weight, and exhibited sufficient structural integrity to be subjectedto subsequent coating steps with various polymers and/or wax, asdescribed below.

To form hydrogel capsules protected with two coating layers, eachcoating layer was sequentially deposited over alginate hydrogel capsulesaccording to the following procedure. Ten alginate hydrogel capsuleswere placed into 10 ml of a 30% aqueous dispersion of Eudragit® (“Eud”)and were shaken gently for 30 seconds. The Eud-coated alginate hydrogelcapsules (“Eud-Alg”) were then physically separated from the aqueousmedium using a sieve. A second coating was obtained by immersing Eud-Alghydrogel capsules into a 12% ACAP solution (12% ACAP-Eud-Alg hydrogelcapsules), or a 24% ACAP solution (24% ACAP-Eud-Alg hydrogel capsules),in acetone with castor oil (3% w/v), respectively, for 10 seconds. Thesedouble-coated hydrogel capsules (“ACAP-Eud-Alg”) were then separatedfrom the solution using a sieve. Both of these concentrations producedworkable viscosities. Castor oil (3% w/v) was added to each solution toprevent the hydrogel capsules from adhering to each other. Acetone maybe employed for facilitate the rate of evaporation during ACAP layerformation at room temperature.

Alternatively, to form hydrogel capsules protected with two coatinglayers, in which one coating layer comprises a wax formulation: 1)Eud-Alg hydrogel capsules were placed in a dry-ice-acetone bath for 1min; 2) the frozen Eud-Alg hydrogel capsules were placed into molten waxand were shaken for 5 seconds; and 3) the wax-coated hydrogel capsules(“Wax-Eud-Alg”) were collected on filter paper and cooled to roomtemperature.

Materials used in the examples include: alginic acid sodium salt (Alg)from brown algae, with the viscosity of a 2% solution at 25° C. being˜250 cps; (acrylamidomethyl)cellulose acetate propionate (ACAP), averageM_(n) ˜20,000 by GPC; carnauba wax, refined, No. 1 yellow (melting point83° C. to 86° C.); granular paraffin waxes (melting points ranging from48° C. to 74° C.) available from Sigma-Aldrich (Sigma-AldrichCorporation, St. Louis, Mo. 63103 USA); Eudragit® L30D-55 (Eud), Mwapprox. 250,000, a methacrylic acid, and ethyl acrylate copolymerdispersion with 30% solids available from Degussa (Röhm America,Piscataway, N.J., USA); and polyester wax available from VWRInternational Ltd. 1310 Goshen Parkway, West Chester, Pa. 19380, USA.

Example 2 Images of Alginate Hydrogel Capsule Coated with Eudragit®L30D-55

FIG. 6A is an image of an exemplary alginate hydrogel capsule coatedwith Eudragit® L30D-55 to form Eud-Alg hydrogel. FIG. 6B is an image ofan exemplary hydrogel capsule, which is first coated with Eudragit®L30D-55, and coated subsequently with a wax formulation to formWax-Eud-Alg hydrogel. Each image contains a scale showing distance inmm. Eudragit® L30D-55 was deposited onto the surface of alginatehydrogel capsules by immersing freshly prepared alginate hydrogelcapsules into an aqueous dispersion of Eudragit® at a pH of 2.5-3.5.Under visual examination, the surface of these Eud-Alg hydrogel capsulesappeared smooth and uniform. Although the principles governing theinteraction between the Eudragit®-dispersed phase and the alginatehydrogel capsules have not been fully characterized, it is conceivablethat, when these hydrogel capsules are immersed in an acidic dispersionof Eudragit®, the negatively charged carboxylate ions of Eudragit® caninteract with the Ca²⁺ present on the surface of alginate hydrogelcapsules, leading to coating formation. The thickness of Eudragit®coating layer can be controlled by adjusting the duration of thereaction and the percentage of Eudragit® included in the aqueousdispersion.

Example 3

Characterization of Eudragit®-Alginate Hydrogel Capsules

FIGS. 7A and 7C show a cross-sectional analysis of Eud-Alg hydrogelcapsule as determined by ESEM. In FIG. 7A, both the core of the alginatehydrogel matrix and the Eudragit® coating layer demonstrated shrinkageafter exposure to a vacuum during sample preparation for ESEM analysis,generating an artifactual void between the alginate hydrogel matrixshell and the Eudragit® coating layer. The Eudragit® coating layerdemonstrated significant mechanical integrity by not collapsing orfracturing in response to the shrinkage of alginate core. In FIG. 7C,the cross-sectional thickness of Eudragit® coating layer was determinedto be about 200 μm. The Eudragit® coating layer also contained Na andCa, and a band rich in Na and Ca appeared to be present about 125 μmfrom the interior surface of the Eudragit® coating layer (arrow).

FIG. 7B is an energy dispersive spectrum (“EDS”) of an Eud-Alg hydrogelcapsule. In FIG. 7B, the alginate contained a significant amount of Caand less substantial amount of Na, suggesting that Ca on the surface ofalginate hydrogel capsules migrated into the Eudragit® coating layerduring the coating process.

FIGS. 7D-7F show cross-sectional analysis of Eudragit® coating todetermine Ca and Na content by x-ray line scans.

The cross-sectional thickness of the Eudragit® coating layer wasdetermined by cross cutting the Eud-Alg hydrogel capsules with a razorblade. The cross cut hemispheres were then placed with the cut face up,onto a 25.4 mm diameter carbon adhesive disk attached to a 32 mmdiameter aluminum stub. Cross sections were imaged using an FEI XL30Environmental Scanning Electron Microscope (ESEM) operating at 15 to 20kV in H₂O vapor mode at a pressure of 0.1 to 1.1 torr. Selected areaelemental analyses were performed on the uncoated cross sections usingthe EDAX energy dispersive spectrometer (EDS) interfaced with the EDAXGenesis software. X-ray line scans were also generated over thefreshly-cut cross sections on the copolymer shells.

Example 4 Surface Morphology of Eudragit®-Coated Alginate Hydrogels

FIG. 8A shows the surface morphology of Eud-Alg hydrogel capsules. InFIG. 8A, the surface of the Eudragit® coating layer appeared to be roughand textured displaying random arrays of submicron pores, less than 3 μmthroughout the samples. Some surface particles appeared to blend intothe surface of the Eudragit® coating layer.

FIG. 8B shows the surface morphology of 12% ACAP-Eud-Alg hydrogelcapsules, in which “ACAP” represents (acrylamidomethyl)cellulose acetatepropionate. In FIG. 8B, the surface of the ACAP coating layer containedan array of circular indentations, or pits. These surface phenomena mayhave been formed by the fast rate of acetone evaporation from the ACAPcoating layer at room temperature.

FIG. 8C shows the surface morphology of thermally treated Eud-Alghydrogel capsules exposed to 120° C. for 5 min. In FIG. 8C, the surfaceof the Eud-Alg hydrogel capsules appeared to be smoother after exposureto 120° C. for 5 min, when compared to the surface appearance of 12%ACAP-Eud-Alg hydrogel capsules as shown in FIG. 8B.

Surface morphological characterization was facilitated by placing thesamples onto 12 mm diameter carbon adhesive disks that were attached toaluminum stubs. The samples were then sputter coated with 15 nm of Au—Pdusing a Cressington 208HR sputter coater operating in argon. An FEI XL30Environmental Scanning Electron Microscope (ESEM) operating at 10 kV inHi-Vac mode was used to obtain photomicrographs.

Example 5 FTIR Analysis of Eudragit® L30D-55 and ACAP-Eudragit CoatingLayers

FIG. 9 shows FTIR graphs for various coating formulations, including acoating layer formulated with (acrylamidomethyl)cellulose acetatepropionate (“ACAP”) (as graph “A”), a coating layer formulated withEudragit® L30D-55 (“Eud”) (as graph “B”), and double-coated layers ofACAP-Eud that were sequentially deposited (as graph “C”). In FIG. 9, thepeaks at wave numbers of 3466 cm⁻¹ and 2929-3021 cm⁻¹ are due to freehydroxyl and intermolecular hydroxyl groups, respectively. The peak at1745 cm⁻¹ is due to ester carbonyls. Other peaks assigned to ACAP: 1685cm⁻¹ (amide group), 1379 cm⁻¹ (—C—N— stretching), 1629 and 805 cm⁻¹ (C═Cstretching). Peaks assigned to Eudragit®: 1160 cm⁻¹ (C—CO—C—stretching), 1385 cm⁻¹ (CH₃— asymmetric bending), 1424 cm⁻¹ (CH₂—symmetric bending) and 1736 cm⁻¹ (C═O stretching). Curve C is a spectrumfrom the ACAP-Eud coating on alginate hydrogel capsules, and shows thepresence of both Eudragit®-specific and ACAP-specific peaks: 1629, 805cm⁻¹ (C═C stretching), 1177 cm⁻¹ (C—CO—C— stretching), 1383 cm⁻¹ (CH₃—asymmetric bending). The shift of C—CO—C— stretching from 1160 cm⁻¹ to1177 cm⁻¹ may be indicative of complex formation or hydrogen bondingbetween ACAP and Eudragit®.

Fourier transform infrared spectroscopy (FTIR) spectra of Eudragit®,ACAP, and ACAP-Eud coating materials were recorded with a Fouriertransform infrared spectrophotometer (Nexus™, 670 FT-IR, Thermo Nicolet)using the KBr disc sampling method. Each sample was gently trituratedwith KBr powder in a sample-to-KBr weight ratio of 1:100, and thenpressed into a disc. The disc was placed in the sample holder andscanned from 4000 to 450 cm⁻¹ at a resolution of 4 cm⁻¹.

Example 6 DSC Analysis of Eud and ACAP-Eud Coating Layers

FIG. 10 shows DSC graphs for various coating formulations, including acoating layer formulated with Eudragit® L30D-55 (as curve “Eud”), acoating layer formulated with (acrylamidomethyl)cellulose acetatepropionate (as curve “ACAP”), and double-coated layers of ACAP-Eud thatwere sequentially deposited (as curve “ACAP-Eud”). In FIG. 10, DSCcurves for the Eudragit® coating layer, the ACAP coating layer, and theACAP-Eudragit® coating layers were measured at the same heating rate.The Eudragit® curve showed a sharp endothermic melting peak at 227° C.The inclination in the graph between 55° C. and 60° C. is related to theglass transition temperature (T_(g)). The apparent T_(g) for ° C. at115° C. reported in the literature was not reproducible in this study,and an additional transition at 125° C. (T_(m)) was observed. Pure ACAPexhibited no apparent T_(g) or T_(m) in the range between −10° C. and290° C. The ACAP-Eud curve exhibited three endothmic peaks at 65° C.,135° C., and 227° C., respectively. These peaks shifted to slightlyhigher temperatures compared to the T_(m) of Eudragit®, and suggestedthe occurrence of possible polymorphic changes after the ACAP coatingformation onto the Eudragit® coating layer.

Differential scanning calorimetry (DSC) curves of the dried Eudragit®layer, ACAP layer, and ACAP-Eud layer were respectively recorded using adifferential scanning calorimeter (DSC Q100/TGA Q500, TA Instruments).Each sample (2-2.5 mg) was weighed and placed into a 40 μl aluminum panwith an aluminum cover. Measurements were performed over a range from−10° C. to 400° C. at a heating rate of 10° C./min.

Example 7 Water Retention of Coated Alginate Hydrogel Capsules

FIG. 11 shows water-retention profiles, expressed as % weight retention,for various hydrogels tested, including alginate hydrogel capsules (“AlgBead”), Eud-coated alginate hydrogel capsules (“Eud-Alg Bead”), alginatehydrogel capsules coated with 12% ACAP solution (“12% ACAP-Eud-AlgBead”), and alginate hydrogel capsules coated with 24% ACAP solution(“24% ACAP-Eud-Alg Bead”) respectively, measured at room conditions of23° C. and RH 50%. In FIG. 11, the loss in water content from alginatehydrogel capsules and from Eud-Alg hydrogel capsules occurred linearlywith respect to storage time. The percentage of water retentiondecreased to less than 40% of the initial water content after 200 min.Nevertheless, a significant reduction in water migration was observed inEud-Alg hydrogel capsules coated with the ACAP coating layer. Watermigration was further reduced as the concentration of the ACAP solutionwas increased from 12% to 24%. For example, the 24% ACAP-Eud-coatedalginate hydrogel capsules exhibited 75% water retention after 200 min,as compared to the 12% ACAP-Eud-coated alginate hydrogel capsules thatexhibited 55% water retention for the same storage period. Thus, anincrease in the ACAP concentration can facilitate the formation of awater-tight layer. Subsequent to complete evaporation of acetone, asolvent-free polymeric coating layer can be formed easily and quickly toprevent further water losses. After exposure for three weeks, the 24%ACAP-Eud-Alg hydrogel capsules demonstrated 29% water retention. It isnoted that any decrease in weight percentage due to solvent losses fromthe various coatings during the drying process were included in thevalue representing total water loss for simplicity. This is reasonablein that the weight of the hydrogel capsule is substantially due to watermolecules impregnated within the alginate matrix. The data supports thatthe disclosed coating formulations can effectuate a significantreduction in water migration and a significant enhancement in waterretention within the coated hydrogel capsules.

The stability of coated alginate hydrogel capsules exposed to roomconditions (23° C., 50% RH) is described as percent of water retention.Namely, values were determined as percent of weight retention of thehydrogel capsules by measuring the weight of individual hydrogelcapsules at regular time intervals via a gravimetric technique and usingthe following equation: % of water retention in a hydrogelcapsule=100%×[W_(ow)−W_(loss)]/W_(ow) (1) in which the W_(ow) is theweight of a newly formed hydrogel capsule (at time zero of theexperiment), and the W_(loss) is the weight loss of a hydrogel capsuleafter a certain period of time. With respect to the ACAP-Eud-Alghydrogel capsule, any weight loss of solvent (acetone) occurring at roomtemperature conditions were considered negligible and thus, included aspart of the total water losses for simplicity.

Example 8 The Effect of pH in Stabilizing Eudragit®-Coated AlginateHydrogel Capsules

FIG. 12 shows short-term (5 hours) and long-term (3 days)water-retention profiles, expressed as % weight retention, forEud-coated alginate hydrogel capsules that were exposed to different pHconditions after coating with Eudragit®, measured at 23° C. and RH 50%.The pH effect on Eud-Alg hydrogel capsules was tested by immersinghydrogel capsules into buffer solutions at various pH values of 1.6,2.4, 3.4, 4.6, and 7.0, respectively, at room temperature for 10seconds. Eudragit® is a pH-dependent, film-forming material that candissolve in water at pH over 5.5.

The Eud-Alg hydrogel capsules were subsequently immersed in HOAc/NaOAcbuffer solutions having pH values ranging from 1.6 to 7.0. Generally, asthe buffer solution is increased in pH, the % of water retention by thehydrogel capsules decreases. For example, at the pH of 1.6, the Eud-Alghydrogel capsules exhibited 40% water retention after three days. Incontrast, at the pH of 4.6, the Eud-Alg hydrogel capsules exhibited 18%at a comparable time point. The pH effect on the water retentioncapacity of Eud-Alg hydrogel capsules can be the result of changes inthe degree of ionization for both Eudragit® and alginate under differentpH conditions. Since the pKa of the Eudragit® carboxylic group is 2.68,the degree of ionization of Eudragit® can change significantly betweenpH 2.4 and 7.0. Moreover, the degree of ionization of alginate (pKaaround 4) can also change in this pH range. At a low pH, Eudragit®ionization decreases. The non-ionized chains of Eudragit® tend to form atighter network, which results in reduced water permeability. At ahigher pH value, the Eudragit® coating can progressively ionize andundergo swelling so that water permeability increases, resulting inwater loss. The data suggests that exposing Eud-Alg hydrogel capsules tolow pH conditions can improve their water retention properties.

FIG. 13A shows the effect on the surface morphology of Eud-Alg hydrogelcapsules exposed to pH 1.6 condition after coating with Eudragit®. At pHvalue of 1.6, the coating layer exhibited tight surface tensionresulting in a lower rate of water loss.

FIG. 13B shows the effect on the surface morphology of Eud-Alg hydrogelcapsules exposed to pH 4.6 condition after coating with Eudragit®. At pHvalue of 4.6, the coating layer appeared to be partially erodedresulting in a higher rate of water loss.

Example 9 Effect of Heat in Stabilizing Eudragit®-Coated AlginateHydrogel Capsules

FIG. 14 shows short-term (5 hours) and long-term (3 days)water-retention profiles, expressed as % weight retention, forEud-coated alginate hydrogel capsules that were exposed to differentthermal exposure after coating with Eudragit®, measured at 23° C. and RH50%. In FIG. 14, higher % water retention within the Eud-Alg hydrogelcapsules was observed for capsules treated at higher temperatures. Heatexposure at 120° C. for 5 min was the most effectivetemperature/duration tested, in that the water retention was 75% after 5hours of aging, and about 59% after 3 days of aging. In addition, the %water retention of the 24% ACAP-Eud-coated alginate hydrogel capsulesafter heat exposure at 60° C. for 10 min was 56% after 5 hours, and 51%after 3 days, measured at 23° C. and 50% RH.

FIG. 15 shows water-retention profiles, expressed as % weight retention,for ACAP-Eud-coated alginate hydrogel capsules that were exposed to 60°C. for 10 min, after coating with Eudragit®, measured at 23° C. and RH50%. The % water retention decreased to 35% after 3 weeks of exposure atroom conditions.

Table 1 below shows the effect of heat exposure on water retentionproperties, expressed as % water loss by weight, for Eudragit® coatingformulations deposited on the surface of alginate hydrogel capsules. Thepercentage of water retained in the various Eud-Alg hydrogel capsulesafter heat exposure ranged from ˜79 to ˜84%. In particular, the exposureof Eud-Alg hydrogel capsules to 40° C. for 10 min can reduce the weightsof the hydrogel capsule by about 13%. Exposure of the Eud-Alg hydrogelcapsules to 60° C. or 80° C. for 10 min, can reduce the weights of thehydrogel capsules by about 27% and 33% of, respectively. Exposure of theEud-Alg hydrogel capsules to 120° C. for 5 min can reduce the weight ofthe capsules by about 32.5%. The 24% ACAP-Eud-Alg hydrogel capsulesexhibited the lowest weight loss after heat exposure at 60° C. for 10min.

In Table 1, “original water content (%)” is [(wet weight−final dryweight)/wet weight]×100%, and “% water in heat-exposed hydrogel capsule”is [original weight of hydrogel capsule×original water %−weight loss ofheat-exposed hydrogel capsule]/[original weight of hydrogelcapsule−weight loss of heat-exposed hydrogel capsule]×100%.

TABLE 1 Original Water Loss Water after heat % Water post- Content Tempexposure heat exposure Beads (%) (° C.) Time (min) (wt. %) (wt. %)Eud-Alg 86 ± 1 40 10 13.6 ± 3 84 ± 3 Eud-Alg 86 ± 1 60 10 27.6 ± 3 81 ±3 Eud-Alg 86 ± 1 80 10 32.9 ± 3 79 ± 3 Eud-Alg 86 ± 1 120 5 32.5 ± 3 79± 3 24% 78 ± 1 60 10  8.3 ± 3 76 ± 3 ACAP- Eud- Alg

The thermal effect may be attributed to increased mobility of thepolymer chains at higher temperatures and to improved consolidation bythe inter-diffusion of polymer chains as Eudragit® particles aggregatewithin the coating layer, driven by capillary action that promotes waterevaporation during thermal exposure. Efficient coating/film formationand efficient coalescence of dispersed latexes can generally be achievedat temperatures above the T_(g) of the latex polymer of Eudragit®. Basedon DSC analysis, phase transitions of Eudragit® were observed at 58° C.and 125° C. When Eud-coated alginate hydrogel capsules were exposed to120° C., which is a higher value than the reported T_(g) value (115°C.), the Eudragit® copolymer can assume a more flexible rubbery statethat can contribute to a more suitable coating/film. Exposing Eud-coatedalginate hydrogel capsules to 120° C. for 5 minutes can induce stressrelaxation and promote the orientation of the Eudragit® copolymer toalter the coating layer morphology conducive in preventing waterdiffusion through the Eudragit® coating.

FIG. 16A shows the surface morphology of ACAP-Eud-Alg hydrogel capsulesnot exposed to heat. In FIG. 17A, an array of circular indentations, orpits were observed on the surface. Larger indentations were usuallyarranged along a linear pathway, and were surrounded by smaller pitsthat were about 20 μm in pore size.

FIG. 16B shows the surface morphology of ACAP-Eud-Alg hydrogel capsulesexposed to 60° C. for 10 min. In FIG. 17B, some significantmorphological changes were observed on the surface of hydrogel capsulessubjected to heat exposure. A large number of randomly shapeddepressions were observed on the surface after 60° C. treatment for 10min. Large depressions were concentrated on the peaks, but as thevalleys were approached, the depressions decreased in size, and werespread over a larger surface area. These depressions were not pores.

The effect of heat on Eud-coated alginate hydrogel capsules orACAP-Eud-coated alginate hydrogel capsules was tested as follows: 1)placing the Eud-Alg hydrogel capsules in an oven at 40, 60 or 80° C.,respectively, for 10 min; 2) placing the Eud-Alg hydrogel capsules in anoven at 120° C. for 5 min; and 3) placing the ACAP-Eud-Alg hydrogelcapsules in an oven at 60° C. for 10 min. Eudragit® has a reported glasstransition temperature (T_(g)) of 115° C. Above T_(g), the mobility ofthe polymer chain increases, and may significantly impact thepermeability of Eudragit® coating. The length of time for each heatexposure was optimized to minimize the water evaporation during theevaluation process.

Example 10 Effect of Heat in Stabilizing Eudragit®-Coated AlginateHydrogel Capsules

FIG. 17 shows water-retention profiles, expressed as % weight retention,for various combinations of coating formulations deposited on thesurface of alginate hydrogel capsules, measured at room conditions 23°C. and RH 50%. In FIG. 17, the Eud-Alg hydrogel capsules not subjectedto pH or heat treated could not effectively inhibit the evaporation ofwater from the alginate gel matrix when compared to uncoated alginatehydrogel capsules (negative control). The 24% ACAP-Eud-coated hydrogelcapsules that were exposed to heat demonstrated improved water retentionproperties with aging, but only moderately.

Table 2 below provides % weight retention measured for variouscombinations of coating formulations plotted in FIG. 18. “Open” sampleswere stored in open trays at room condition 74° F. and 50% RH. “Close”samples were stored at room condition 74° F. and 50% RH in 32 ml vialswith snap caps

TABLE 2 Water Retention (%) with Storage at 74° F. (23° C.) and 50% RH 1week 2 weeks 3 weeks 4 weeks 5 weeks Bead Type Open Close Open CloseOpen Close Open Close Open Close Alginate alone 0 87 0 74.3 0 66.6 053.4 0 21.7 Eud-coated 0 91.6 0 81.5 0 74.1 0 61.3 0 57.5Polyesterwax-Eud 95.6 — — — — — — — — — Carnaubawax-Eud 97.6 — 96.5 —95.6 — 94.8 — 93.9 — Paraffinwax-Eud 100 — 100 — 100 — 100 — 100 — WaterRetention (%) with Storage at 74° F. (23° C.) and 50% RH 7 weeks 9 weeks11 weeks 13 weeks 15 weeks Bead Type Open Close Open Close Open CloseOpen Close Open Close Alginate alone 0 0 — 0 — 0 — 0 — Eud-coated 0 0 —0 — 0 — 0 — Polyesterwax-Eud — — — — — — — — — — Carnaubawax-Eud — — — —— — — Paraffinwax-Eud 100 — 100 — 100 — 100 — 100 —

The wax coatings significantly improved the percent water retention. Thetype of wax selected can make a significant contribution to theeffectiveness of the coating in preventing water loss.Polyester-wax-coated hydrogel capsules exhibited 95.6% water retentionafter one week of aging. In contrast, carnauba-wax-coated hydrogelcapsules exhibited 97.6% water retention after the same time period.Paraffin wax, however, formed the most effective water-impermeablecoating layer, as the Paraffin Wax-Eud-coated alginate hydrogel capsulesdemonstrated almost 100% water retention when left in an open tray at23° C. and 50% RH for fifteen weeks (three months). Wax is highlyhydrophobic and contains large content of long-chain alkanes. A coatinglayer comprising a wax formulation can be effective in forming alow-permeability coating layer that can be deposited onto the surface ofhydrogel capsules containing a substantial amount of water. Any naturalpolymer can be employed for producing the hydrogel matrix, such asalginate, to serve as a carrier of water, water-soluble flavors, orwater-soluble active agent of interest. The hydrogels enveloped by thedisclosed coating formulations exhibit desirable properties, includingmechanical strength and low-permeability. Unlike the film-coatingprocesses described herein for the formation of latex-like/polymercoatings, the dip-wax coating process does not require the use ofsolvents that may lead to environmental problems, solvent residues, orexcessive recovery costs.

It will be appreciated that, although specific embodiments of theinvention have been described herein for purposes of illustration,various modifications may be made without departing from the spirit andthe scope of the invention. Accordingly, the invention is not limitedexcept as by the appended claims. Unless defined otherwise, alltechnical and scientific terms have standard meaning as commonlyunderstood to persons skilled in the art. Although exemplary methods,devices, and materials have been described with particularity,alternative methods and materials, that may be similar or equivalent tothose described herein, are applicable for making the disclosedcompositions and for practicing the disclosed methods.

1. A method of preparing capsules with improved water retention,comprising: preparing hydrogel capsules having a diameter of 1 to 5 mmand comprising one or more optional additives and a polymer selectedfrom the group consisting of alginates, pectins, carrageenan; applying apolymeric coating to the capsules; and treating the polymeric coatingand optionally applying a second coating to form capsules with improvedwater retention that exhibit water retention of at least 40% after threedays at 23 degrees C. and 50% relative humidity.
 2. The method of claim1, wherein the treating comprises contacting with a solution having a pHbelow
 5. 3. The method of claim 1, wherein the treating comprises heattreatment at a temperature above a glass transition temperature of thepolymeric coating.
 4. The method of claim 3, wherein the heat treatmentcomprises heating in air for at least 5 minutes at a temperature of atleast 60 degrees C. or at least 120 degrees C.
 5. The method of claim 1,further comprising applying the second coating.
 6. The method of claim5, wherein the second coating is a wax coating.
 7. The method of claim6, wherein the wax is selected from the group consisting of polyesterwax, carnauba wax, and paraffin wax.
 8. The method of claim 6, whereinsaid applying the second coating comprises freezing the capsules havingthe polymeric coating and contacting the frozen capsules with moltenwax.
 9. The method of claim 5, wherein the second coating comprises(acrylamidomethyl)cellulose acetate propionate.
 10. The method of claim1, wherein the polymeric coating is formed from a methacrylic acid andethyl acrylate copolymer dispersion with 30% solids.
 11. The method ofclaim 1, wherein the polymeric coating is of (acrylamidomethyl)celluloseacetate propionate.
 12. The method of claim 1, wherein the capsulecomprises an additive selected from the group consisting of flavorants,tobacco, antioxidants, medicaments, nutraceuticals, cell culture medium,cosmetics, agrochemicals, disinfectants, detergents, and dyestuff. 13.The method of claim 1, wherein the capsules exhibit water retention ofat least 90% after three days at 23 degrees C. and 50% relativehumidity.
 14. The method of claim 1, wherein the polymer is alginate.15. A capsule comprising: a core comprising gelled alginate and one ormore optional additives and having a diameter of 1 to 5 mm, a polymericcoating substantially surrounding the core, and an optional secondcoating, wherein the capsule exhibits water retention of at least 40%after three days at 23 degrees C. and 50% relative humidity.
 16. Asmoking article or smokeless tobacco product incorporating one or morecapsules according to claim
 15. 17. The product according to claim 16,wherein the product is a smokeless tobacco product and the smokelesstobacco is contained in a porous wrapper.
 18. An orally consumabletobacco-free product incorporating one or more capsules according toclaim
 15. 19. The product according to claim 16, wherein the product isa cigarette, and the one or more capsules is incorporated in a tobaccorod and/or a filter of the cigarette.
 20. The product according to claim16, wherein the product is moist smokeless tobacco.
 21. The capsuleaccording to claim 15, comprising an additive selected from the groupconsisting of flavorants, tobacco, antioxidants, medicaments,nutraceuticals, cell culture medium, cosmetics, agrochemicals,disinfectants, detergents, and dyestuff.